Interspecies variation in myocardial physiology: the anomalous rat

THE HEART OF THE ADULT RAT HAS LONG BEEN RECOGNIZED TO BE ANOMALOUS IN AT LEAST TWO RESPECTS: an absent or negative inotropic response to an increase in rate of electrical stimulation (negative staircase); resistance to digitalis glycosides. The heart of the neonatal rat (less than 2 weeks old), on the other hand, demonstrates a markedly positive staircase and a large increase in force upon application of glycoside. It is significant that the action potential of the neonate ventricle demonstrates a prolonged plateau component which progressively decreases with age. The shortening of the plateau correlates with the disappearance of the positive staircase and glycoside responses. Previous studies indicated that a major factor contributing to the prolonged plateau of the neonate was a high level of sodium (Na) conductance. Thus transmembranous Na movement associated with excitation is considerably greater in the neonatal heart as compared to the heart of the adult rat. The higher level of intracellular Na would produce increased activity of a proposed sodium-calcium (Na-Ca) carrier. This is believed to mediate the augmented influx of Ca which is responsible for positive staircase and glycoside responses. Ventricular muscle from the hearts of most mammalian species demonstrates a prolonged plateau with maintenance of a "slow" channel for Na. It appears that in the rat this channel closes with age. It follows that there would be a reduced tendency for the adult rat heart to accumulate intracellular Na, [Na](i), when excitation frequency is increased or the Na pump is inhibited by digitalis. Since elevation of [Na](i) is the stimulus for the proposed Na-Ca carrier, this system would not be activated, Ca influx would not increase and contractility would not be augmented.